Chapter 6: Sleep

In this Chapter:

• Brain Activity during Sleep
• Sleep disorders
• How is sleep regulated?
• The Sleep-Wakefulness Cycle

Introduction

• Lack of sleep increases the risk of many health problems including:   * Diabetes   * Cardiovascular disease   * Heart attacks   * Stroke   * Depression   * High Blood Pressure/Hypertension   * Obesity   * Infections
• Sleep is made of several different stages that are accompanied by daily rhythms in hormones, body temperature, etc.
• Sleep disorders are one of the least recognized sources of disease, disability, and death

Brain Activity During Sleep

• $Electroencephalography (EEG)$: the measurement of electrical activity in different parts of the brain and the recording of such activity as a visual trace (on paper or on an oscilloscope screen).
• One sleep cycle is approximately 90 minutes
• Each night, the brain progresses through a series of stages when brain waves slow down for 60 minutes in NREM (non-rapid eye movement) sleep   * This is accompanied by the relaxation of muscles and eyes   * Heart rate, Blood pressure, and body temperature fall   * If awakened in this stage of sleep, most people only recall fragments of thought   * $NREM sleep$: sleep where the eyes do not rapidly move
• Over the next half-hour, brain activity changes to REM sleep   * $REM (Rapid Eye Movement) sleep:$ sleep characterized by the random rapid movement of the eyes when derams also occur   * Characterized by neocortical (in the neocortex) EEG waves similar to those when a person is awake   * REM is accompanied by atonia     * $Atonia$: paralysis of muscle   * Dreaming occurs only in REM sleep     * The first REM period lasts 10-15 min
• Over the course of one’s lifetime: slow-wave sleep time decreases & REM time increases
• Overall sleeping time at different life stages:   * Infants: up to 18 hrs   * Older adults: 6-7 hrs     * Less time sleeping in general and in slow wave sleep specifically

Sleep Disorders

• $Insomnia$: the most common sleep disorder where individuals have trouble falling asleep   * Some people have problems falling asleep, some wake up in the middle of the night and can’t fall asleep again   * Sleeping drugs do not help because they suppress slow-wave sleep and aren’t effective in keeping people asleep
• Many common disorders disrupt deeper stages of sleep
• Excessive daytime sleepiness has many causes   * $Obstructive Sleep Apnea$: airway muscles relax and close airway causing difficulty breathing     * individual wakes up without entering deeper stages of slow-wave sleep.     * Causes high blood pressure and increases the risk of heart attack     * more daytime sleepiness   * $Periodic Limb Movements$: intermittent jerks of the legs or arms that occur as individual enters slow wave sleep and cause arousal from sleep.   * $REM behavior disorder$: occurs when muscles fail to become paralyzed during REM sleep     * Act out dreams by getting up and moving around.     * Can be very disruptive.   * Both periodic limb movements and REM behavior disorder are more common in people with Parkinson’s disease.     * Can be treated with drugs for Parkinson’s or with a benzodiazepine called clonazepam
• $Narcolepsy$: mechanisms controlling transitions into sleep (particularly REM sleep) don’t work.   * Narcolepsy is caused by the loss of nerve cells in lateral hypothalamus that contain orexin/hypocretin.     * Have sleep attacks during day (suddenly fall asleep).     * $Hypnagogic hallucination$: individuals tend to enter REM sleep very quickly and enter dreaming state while partially awake     * $Cataplexy:$ loss of muscle tone similar to what happens in REM sleep but occurs when the individual is still awake

How is Sleep Regulated?

• Wakefulness is maintained by systems in the upper brainstem and hypothalamus   * Neurons here use acetylcholine, norepinephrine, serotonin, glutamate to connect with the forebrain   * Neurons in the hypothalamus use orexin and some contain histamine   * Thalamus and basal forebrain activation by acetylcholine is very important too     * basal means “closest to midbrain/base”
• Level of alertness can be shown in an activated low-volt EEG
• Arousing systems are less active in non-REM sleep   * Transmission of information to the thalamus is limited
• Ventrolateral preoptic (VLPO) nucleus: area in the brain that causes suppression of arousal systems   * VLPO nucleus neurons have the inhibitors galanin and GABA   * Damage to the VLPO area produces irreversible insomnia
• In REM sleep, there is an internally activated brain and EEG but the external input is suppressed   * Internal activation comes from cyclically active REM sleep generator neurons in the brainstem
• Signals from neurons cause the excitation of the forebrain   * Leads to rapid eye movements & muscle suppression
• Forebrain excitation driving force behind dreams of REM sleep
• Motor cortex neurons fire as rapidly during REM sleep as during waking movement   * Explains movement coinciding with dreams
• Periodic recurrence of REM sleep   * REM sleep occurs every 90 min during sleep   * This is caused by on-and-off switching of REM-generators (acetylcholine, glutamate) and REM-suppressors (norepinephrine, serotonin, GABA)

The Sleep-Wakefulness Cycle

• 2 determining factors for sleepiness:   * $Circadian system$: Monitoring the time of day/night   * $Homeostatic system$: monitoring how long the person is awake
• Circadian system is regulated by the suprachiasmatic nucleus   * $Suprachiasmatic nucleus$: a small group of cells in the hypothalamus serving as the master clock     * It expresses clock proteins that go through a biochemical cycle of approximately 24 hrs     * This sets the pace for daily cycles of activity, sleep hormone release, etc.
• The suprachiasmatic nucleus also receives input from the retina   * The clock can be reset by light so it is linked to the outside day-night cycle
• Also provides information to the subparaventricular nucleus → dorsomedial nucleus → VLPO and orexin neurons   * $Orexin$: an excitatory signal to arousal system especially norepinephrine neurons     * Orexin activation plays role in preventing transitions into REM sleep during the day
• Arousal mediated by orexin and activation of norepinephrine neurons in the locus coeruleus   * $Locus coeruleus$: a lateral part of brain stem that has norepinephrine producing neurons that mediate arousal along with orexin
• The homeostatic system responds to longer wake periods by increasing the urge to sleep   * The longer a person is awake, the greater the likelihood of an increase in sleep-inducing factors
• $Adenosine$: a very important sleep promotor   * More adenosine means increased sleepiness   * Adenosine release starts in the basal forebrain and spreads to the rest of the cortex   * Increased adenosine levels slow down cellular activity and diminish arousal   * Adenosine levels decrease during sleep
• Brain adenosine may be produced by ATP breakdown over the course of wakefulness
• Neuron activity decreases and adenosine levels decline in non-REM sleep   * ATP levels increase during sleep

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